Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among males. Epidemiological studies show that persons of African-American descent have a higher incidence of clinically significant cases than can be explained by socioeconomic and environmental factors. Cultures whose diets are high in soy products are associated with a low incidence of prostate cancer. Soy products are particularly rich in isoflavones, a class of naturally occurring phytoestrogens. The isoflavones biochanin A and genistein have been shown to inhibit the growth of human prostate cancer cells in vitro, as well as the proliferation of a number of other human cancer cells. The proposed research will use a molecular epidemiological approach for the development of biomarkers of prostate cancer risk and for utilization in chemoprevention studies. The effects of dietary isoflavones on the biologic behavior of human prostate tumor growth will be evaluated in human prostate cancer cells in culture and tissue from prostate cancer patients. Experiments with human tissue will use paired samples of nonmalignant prostate tissue and tumor samples with known histopathology. The hypothesis is that dietary isoflavonoids will suppress prostatic hyperproliferative pathology through changes in the expression of specific genes. The overall goal is to determine whether the molecular biomarkers identified in established human prostate cell lines are valid in human tissue samples. The first Specific Aim will use cDNA microarray analysis to compare alterations in gene expression in cultured human prostate cancer cell lines treated either with individual isoflavones or a soy phytochemical concentrate. The second Specific Aim will evaluate whether the genes altered by isoflavonoids in the cell lines are also expressed in human benign and malignant prostatic tissue of various tumor grades. Molecular epidemiological analyses will be done to determine if populations at risk for prostate cancer, such as African-Americans, have different expression patterns from Caucasians. This may help assess the potential therapeutic use of isoflavonoids in prostate cancer treatment regimens.